The use of HMG-CoA reductase inhibitors is contraindicated in patients with active liver disease or unexplained, persistent elevations of serum transaminases. HMG-CoA reductase inhibitors are extensively metabolized by the liver. Decreased drug metabolism may lead to accumulation and increased risk of toxicity, including biochemical abnormalities of liver function and, rarely, jaundice, hepatitis, cirrhosis, fatty change in the liver, and fulminant hepatic necrosis. Therapy with HMG-CoA reductase inhibitors should be administered cautiously in patients with a history of liver disease and/or heavy alcohol use. A lower initial dosage may be appropriate, and clinical monitoring of liver transaminase levels according to the individual product package labeling is recommended. Patients who develop elevated ALT or AST levels during therapy should be monitored until abnormalities resolve. If an increase above 3 times the upper limit of normal persists, consideration should be given to a reduction in dosage or withdrawal of therapy.

Severe myopathy, including rhabdomyolysis with acute renal failure secondary to myoglobinuria, has been reported rarely with the use of HMG-CoA reductase inhibitors. The myopathy may be dose-related and is characterized by muscle aches and/or weakness in conjunction with increases in creatine phosphokinase (CPK) values exceeding 10 times the upper limit of normal. Therapy with HMG-CoA reductase inhibitors should be administered cautiously in patients with preexisting myopathy, in those with predisposing factors for myopathy or with a history of myoneural disorder, since it may delay the recognition or confound the diagnosis of a drug-induced musculoskeletal effect. Patients should be advised to report promptly any unusual muscle pain, tenderness or weakness, particularly if accompanied by malaise or fever. Periodic CPK determinations may be considered in some patients, although the value of such monitoring is uncertain. HMG-CoA reductase inhibitor therapy should be withdrawn if markedly elevated CPK levels occur or if drug-related myopathy is diagnosed or suspected.

Lovastatin (Includes Lovastatin/niacin) ↔ Renal Dysfunction

Severe Potential Hazard, High plausibility

Applies to: Renal Dysfunction

In patients with severe renal impairment (CrCl < 30 mL/min.), the plasma concentrations of total HMG-CoA reductase inhibitors after a single dose of lovastatin may be approximately two-fold higher than those in healthy patients, presumably due to the accumulation of active metabolites. Increased HMG-CoA reductase inhibitory activity may be associated with a greater risk of adverse effects, including hepatic and musculoskeletal toxicities. Therefore, lovastatin dosage increases above 20 mg/day should be considered and implemented cautiously in patients with severe renal impairment. Close clinical monitoring is recommended during therapy.

The Coronary Drug Project (1975) reported a significant increase in cardiac arrhythmias associated with the use of niacin at lipid-lowering dosages. Treatment using pharmacologic dosages of niacin and niacinamide (nicotinamide) should be administered cautiously in patients with coronary heart disease or arrhythmias. Particular caution is advised in the presence of unstable angina or in the acute phase of myocardial infarction, especially if the patient is also receiving vasoactive drugs such as nitrates, calcium channel blockers, or adrenergic blocking agents.

Niacin/Niacinamide (Includes Lovastatin/niacin) ↔ Hepatotoxicity

Severe Potential Hazard, High plausibility

Applies to: Liver Disease, Alcoholism, Gallbladder Disease

The use of nicotinic acid and its derivatives at dosages substantially exceeding those for physiologic requirements is contraindicated in patients with active liver disease or unexplained, persistent elevations of serum transaminases. Hepatotoxicity, including biochemical abnormalities of liver function, cholestatic jaundice, increased prothrombin time, and fulminant hepatic necrosis and failure, has been reported during therapy with niacin and niacinamide (nicotinamide), particularly in patients who have substituted sustained-release nicotinic acid products for immediate-release preparations at equivalent dosages. Treatment using pharmacologic dosages (e.g., lipid-lowering dosages) of these agents should be administered cautiously in patients with gallbladder disease or a history of jaundice, liver disease and/or heavy alcohol use. Liver transaminase levels should be evaluated prior to initiation of therapy, every 6 to 12 weeks for the first year, and periodically thereafter (e.g., semiannually). Patients who develop elevated ALT or AST levels during therapy should be monitored until abnormalities resolve. If an increase above 3 times the upper limit of normal persists, therapy should be withdrawn. Liver biopsy should be considered in patients with elevations that persist beyond cessation of therapy.

Niacin/Niacinamide (Includes Lovastatin/niacin) ↔ Hypotension

Severe Potential Hazard, High plausibility

Applies to: Hypotension, Syncope

The use of niacin and niacinamide (nicotinamide) is contraindicated in patients with severe hypotension. These agents have peripheral vasodilating effects and may commonly cause flushing at dosages substantially exceeding those for physiologic requirements (e.g., lipid-lowering dosages).

The use of niacin and niacinamide (nicotinamide) at dosages substantially exceeding those for physiologic requirements is contraindicated in patients with active peptic ulcer disease. These agents have been reported to activate peptic ulcer. Treatment using pharmacologic dosages (e.g., lipid-lowering dosages) should be administered cautiously in patients with a history of peptic ulcer disease.

Cognitive impairment (e.g., memory loss, forgetfulness, amnesia, memory impairment, confusion) have been observed in patients receiving statins. The reports are usually not serious, and reversible upon statin discontinuation. Caution is recommended when using these agents in patients with cognitive impairment.

Moderate

Hmg-Coa Reductase Inhibitors (Includes Lovastatin/niacin) ↔ Diabetes

Moderate Potential Hazard, Moderate plausibility

Applies to: Diabetes Mellitus

Increases in HbA1c and fasting serum glucose levels have been reported with the use of certain HMG-CoA reductase inhibitors. Caution should be exercised when using these agents in diabetic patients and close monitoring is recommended.

Moderate

Niacin/Niacinamide (Includes Lovastatin/niacin) ↔ Hyperglycemia

Moderate Potential Hazard, Moderate plausibility

Applies to: Diabetes Mellitus

Elevated fasting blood sugars and decreased glucose tolerance have been reported during niacin and niacinamide (nicotinamide) therapy at dosages substantially exceeding those for physiologic requirements. Patients with diabetes mellitus should be monitored more closely during therapy with these agents, and adjustments made accordingly in their antidiabetic regimen.

Niacin/Niacinamide (Includes Lovastatin/niacin) ↔ Hyperuricemia

Moderate Potential Hazard, Moderate plausibility

Applies to: Gout

Large doses of niacin and niacinamide (nicotinamide) can compete with uric acid for excretion by the kidney. Hyperuricemia and precipitation of gout have been reported during long-term therapy. Treatment using pharmacologic dosages (e.g., lipid-lowering dosages) of these agents should be administered cautiously in patients with or predisposed to gout.

Do not stop taking any medications without consulting your healthcare provider.

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How to Prevent Deadly Drug Interactions

Some mixtures of medications can lead to serious and even fatal consequences.